Showing papers by "University of Münster published in 1996"

Human Y Chromosome Azoospermia Factors (AZF) Mapped to Different Subregions in Yq11

Abstract: In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia wereanalysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involvingseveral DNA loci, while an additional patient had an inherited deletion. They were mapped to three differentsubregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second andthird subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletionsobserved were not overlapping but the extension of the deleted Y DNA in each subregion was similar in eachpatient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phasewhen the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletionoccurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesisloci in Yq11 and that each locus is active during a different phase of male germ cell development. As the mostsevere phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc.Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed. INTRODUCTIONGenes for male germ cell development are present on the Ychromosome in different species groups (1–3). In men, theposition of a spermatogenesis locus was mapped in theeuchromatic part of the long Y arm (Yq11). It was called‘azoospermia factor’ (AZF), as the first six men observed withterminal deletions in Yq were azoospermic (4). Mature spermcells were not detectable in their seminal fluid. In all cases, the Ydeletions included the large heterochromatin block of the long Yarm (Yq12) and an undefined amount of the adjacent euchromatin(Yq11). Subsequently, the presence of AZF in Yq11 wasconfirmed by numerous studies at both cytogenetic (5) andmolecular level (6–8). However, the genetic complexity of AZFcould not be revealed by these analyses.This first became possible by the detection of sterile patientswith small interstitial deletions (i.e. microdeletions) in Yq11. Ina study with 13 sterile men suffering from idiopathic azoospermiatwo different microdeletions in Yq11 were observed (9). Theywere mapped to two non overlapping positions in Yq11 interval6 (10). However, further studies of Yq11 microdeletionsassociated to the phenotype of male sterility, only confirmed theposition of an AZF locus in distal Yq11 (11,12). The mostextensive study was performed by Reijo et al. (13) on 89 sterile

A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation

Abstract: Mycopehenolate mofetil (MMF) is a powerful immunosuppressant that inhibits the proliferation of T and B lymphocytes by blocking the enzyme inosine monophosphate dehydrogenase. MMF has been shown to prevent acute graft rejection in animal experiments and may have an important role in clinical renal transplantation. We conducted a prospective, double-blind, multi-center trial to compare the efficacy and safety of MMF and azathioprine within standard immunosuppressive regimen for patients receiving a first or second cadaveric renal graft. A total of 503 patients were randomized to groups receiving MMF 3 g (n=164), MMF 2 g (n=173), or azathioprine (AZA) 100-150 mg (n=166) daily. All were treated simultaneously with equivalent doses of cyclosporine and oral corticosteroids and followed for 12 months. The primary endpoint was treatment failure, defined as the occurrence of biopsy-proven graft rejection, graft loss, patient death, or discontinuation of the study drug during the first 6 months after transplantation. Treatment failure occurred in 50.% of patients in the AZA group by 6 months after transplantation, compared with 34.8% in the MMF 3g group (P=0.0045) and 38.2 % in the MMF 2g group (P=0.0287). Biopsy-proven rejection occurred in 15.9% of patients in the MMF 3 g group and 19.7% in the MMF2 g group, compared with 35.5% in the AZA group. Rejection of histologic severity grade II or more developed in 6.1 %, 10.4% and 19.9% of patients in the MMF 3 g, MMF 2 g, and AZA groups, respectively. Patients receiving MMF required less frequent and less intensive treatment for acute rejection: 24.4% of patients on MMF 3 g and 31.0% on MMF 2 g were tested for acute rejection, compared with 47.5% on AZA. Only 4.9% on MMF 3 g and 8.8% on MMF 2 g required antilymphocyte antibodies for treatment of severe or steroid-resistant rejection, compared with 15.4% of the patients on AZA. At 1 year after transplantation, graft survival in the MMF groups was marginally superior to that in the AZA group, although this difference was not statistically significant. Gastrointestinal toxicity and tissue-invasive cytomegalovirus infection were more common in the MMF 3 g group. Noncutaneous malignancies occurred in six patients on MMF 3 g, three patients on MMF 2 g, and four patients on AZA. Lymphoproliferative disorders occurred in two patients per MMF group, compared with one patient receiving AZA. MMF appears to be an important advance in prophylaxis following renal transplantation. It is associated with a significantly lower rate of treatment failure compared with AZA during the first 6 months after renal transplantation and produces a clinically important reduction in the incidence, severity, and treatment of acute graft rejection. These differences persist throughout the first year of follow-up. Clinical benefit was greatest with a dose of MMF 3 g/day, but gastrointestinal effects, invasive cytomegalovirus infection, and malignancies were slightly more common at that dose. The appropriate dose may lie between 2 g and 3 g per day and may require individualization depending on clinical course or other factors.

Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: Implications for gene therapy

Abstract: The development of stem–cell gene therapy is hindered by the absence of repopulation assays for primitive human hematopoietic cells. Current methods of gene transfer rely on in vitro colony–forming cell (CFC) and long–term culture–initiating cell (LTC–IC) assays, as well as inference from other mammalian species. We have identified a novel human hematopoietic cell, the SCID–repopulating cell (SRC), a cell more primitive than most LTC–ICs and CFCs. The SRC, exclusively present in the CD4+ CD8− fraction, is capable of multilineage repopulation of the bone marrow of nonobese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice). SRCs were rarely transduced with retroviruses, distinguishing them from most CFCs and LTC–ICs. This observation is consistent with the low level of gene marking seen in human gene therapy trials. An SRC assay may aid in the characterization of hematopoiesis, as well as the improvement of transduction methods.

Severe impairment of spermatogenesis in mice lacking the CREM gene

Abstract: SPERMATOGENESIS is a complex developmental process that occurs in several phases. A large number of genes have been identified that are expressed during spermatogenesis1,2, but the biological significance of many of these is not yet known. We have used gene targeting to selectively eliminate the transcription factor CREM (cyclic AMP-responsive element modulator), which is thought to e important for mammalian spermatogenesis3–5. Male mice deficient for all CREM proteins are sterile, as their developing spermatids fail to differentiate into sperm, and postmeiotic gene expression in the testis declines dramatically. The cessation of sperm development is not accompanied by decreases in the levels of follicle-stimulating hormone or testosterone. Our findings indicate that the CREM gene is essential for spermatogenesis, and mice deficient for this transcription factor could serve as a model system for the study of idiopathic infertility in men.

A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).

Abstract: X-linked retinitis pigmentosa (xlRP) is a severe progressive retinal degeneration which affects about 1 in 25,000 of the population. The most common form of xlRP, RP3, has been localised to the interval between CYBB and OTC in Xp21.1 by linkage analysis and deletion mapping. Identification of microdeletions within this region has now led to the positional cloning of a gene, RPGR, that spans 60 kg of genomic DNA and is ubiquitously expressed. The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase. The C-terminal half contains a domain, rich in acidic residues, and ends in a potential isoprenylation anchorage site. The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene.

Hypertriglyceridemia and elevated lipoprotein(a) are risk factors for major coronary events in middle-aged men

Abstract: Cardiovascular risk factors were analyzed in 4,849 male participants, aged 40 to 65 years, in an 8-year follow-up of the Munster Heart Study (Prospective Cardiovascular Munster Study; PROCAM). One hundred eighty-one definite nonfatal myocardial infarctions, 49 fatal myocardial infarctions, and 28 sudden cardiac deaths were observed. Multiple logistic function analysis confirmed that age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, cigarette smoking, diabetes mellitus, angina pectoris, and family history of myocardial infarction were important cardiovascular risk factors. Interestingly, this analysis revealed a significant and independent association between serum levels of triglycerides and the incidence of major coronary events. The relation between lipoprotein(a) [Lp(a)] levels and the occurrence of major coronary events was analyzed in a subgroup of 878 men. Thirty-three probands with major coronary events had significantly higher geometric mean levels of Lp(a) than 828 men who did not experience major coronary events (0.09 vs 0.05 g/L; p <0.011). Thus, in addition to established risk for factors, serum levels of triglycerides and Lp(a) are sensitive indicators of increased risk major coronary events.

Accuracy of pedicle screw placement in lumbar vertebrae.

Abstract: Study design: The location of pedicle screws (n = 42) in four human specimens of the lumbar spine and in 30 patients (n = 131 screws) after lumbar spinal fusion was assessed using computed tomography. Objectives: To determine the accuracy of pedicle screw placement in lumbar vertebrae and the reproducibility and repeatability of the computed tomography examination. Summary of background data: Failures in the placement of transpedicular screws for lumbar fusion are reported. The evaluation of such screws using computed tomography examination has not been investigated. Methods: After surgery, the specimens were dissected in transversal slices to observe macroscopically the location of the pedicle screw and to correlate these observations with the computed tomography images. All patients were examined by one observer. To determine the reproducibility and repeatability of the computed tomography examination, two observers studied computed tomography images of 12 patients (n = 58 screws) twice within 3 months. Results: In the specimens, 10 screws were observed to penetrate the medial wall of the pedicle. This correlated fully with the images. In the patients' group, 40% of all screws penetrated the cortex of the vertebra. Of all screws, 29% penetrated the medial wall of the pedicle. From the computed tomography images, it appeared that a deviation of more than 6 mm medially was a high risk for nerve root damage. Three months after his first examination, Observer 1 documented a different position in three of 58 screws (kappa = 0.90). Observer 2 found a different position in eight screws (kappa = 0.65). The comparison between the reviews of the two observers showed a different opinion for the first evaluation, four disagreements (2-4 mm) and 17 disagreements (0-2 mm; kappa = 0.34), and for the second evaluation, four disagreements (2-4 mm) and 12 disagreements (0-2 mm; kappa = 0.43). Conclusions: Correct placement of transpedicular screws for spinal fusion seems to be more difficult than it looks. The computed tomography scanning is useful for differential diagnosis of postoperative radicular syndromes after lumbar transpedicular fixation.

Surgical cure for early rectal carcinomas (T1). Transanal endoscopic microsurgery vs. anterior resection.

Abstract: PURPOSE: This study was undertaken for the comparison of local resection for early rectal carcinomas using transanal endoscopic microsurgery or anterior resection. METHODS: Data from 50 of 52 patients with proven adenocarcinoma (GI/II) and intraluminal ultrasound with Stage uT1 N negative (uTNM) were evaluated in a prospective randomized study with two therapeutic arms: transanal endoscopic microsurgery (TEM; n=24) or anterior resection (AR; n=26), performed under general anesthesia. RESULTS: Patients' ages and rectal tumor locations showed insignificant differences of distribution in comparison of TEM with AR (Welsh's alternatet-test;t-test). Local recurrence (4.2 percent) and five-year survival rates (96 percent) differed insignificantly (log-rank test). Early postoperative mortality was zero. Significant differences were found comparing time of hospitalization, loss of blood, operation time, and opiate analgesia (Welsh's alternatet-test; Wilcoxon's test; eachP< 0.05). Early and late morbidity differed considerably. CONCLUSIONS: Lower morbidity, similar local recurrence, and survival rates favor the TEM technique. Comparable results in survival rate to the gold standard (AR) are objective arguments for choosing the adequate surgical procedure. For early rectal cancer, the minimum invasive TEM technique should be preferred because of superior overview during operation with safer suturing after meticulous full wall thickness excision.

TBT-induced imposex in marine neogastropods is mediated by an increasing androgen level

Abstract: Tributyltin (TBT) exposure at different concentrations (5, 60, and 100 ng TBT as Sn/l) induces a concentration- and time-dependent imposex (=pseudohermaphroditism) development in femaleNucella lapillus andHinia reticulata. In both species the average imposex stage, termed as vas deferens sequence (VDS) index, and the average female penis length increases with increasing TBT concentration and duration of TBT exposure. Testosterone added at a concentration of 500 ng/l induces a faster and more intensive imposex development compared to that induced by the TBT concentrations used in the present experiments. Radioimmunological determination of endogenous steroid content reveals increasing testosterone titres in female gastropods exposed to TBT which correlate with the TBT concentration used and the duration of the experiment. The most marked and highest increase of the endogenous testosterone level is exhibited by females, of both species exposed to testosterone. Simulataneous exposure to TBT and to the antiandrogen cyproterone acetate which suppresses imposex development completely inN. lapillus and reduces imposex development strongly inH. reticulata proves that the imposex-inducing effects of TBT are mediated by an increasing androgen level and are not caused directly by the organotin compound itself. Further-more, TBT-induced imposex development can be suppressed in both snails by adding estrogens to the aqueous medium. These observations suggest that TBT causes an inhibition of the cytochrome P-450 dependent aromatase system which catalyses the aromatization of androgens to estrogens. The increase of the androgen content or the shift of the androgen-estrogen balance in favour of androgens induces the development of pseudohermaphroditism in marine prosobranchs. Artificial inhibition of the cytochrome P-450 dependent aromatase system using SH 489 (1-methyl-1,4-androstadiene-3,17-dione) as a steroidal aromatase inhibitor and flavone as a nonsteroidal aromatase inhibitor induces imposex development inN. lapillus as well as inH. reticulata.

Remifentanil: a novel, short-acting, mu-opioid.

Abstract: Because of remifentanil's unique pharmacokinetics, its systemic administration may be suitable for clinical settings where a potent, fast-acting, systemic mu-opioid with a rapid recovery is required, e.g., short painful intervention in the emergency room or the intensive care unit, or procedures in the day surgery or endoscopy suite. Total intravenous anesthesia for longer lasting procedures may become more promising because of the predictability of the offset of remifentanil even after long infusions. Its closest competitor, alfentanil, depends on its small volume of distribution for rapid termination of its effect, but still possesses the potential to accumulate because of its relatively long terminal elimination half-life. Remifentanil might be the first potent mu-opioid that does not accumulate in this fashion, and therefore it opens promising new clinical perspectives (52). However, as mentioned above, the relative short-lasting analgesic effect after cessation of the remifentanil infusion might require new, sophisticated techniques from the anesthetist to prevent immediate onset of postoperative pain.

Synchronous GABA-Mediated Potentials and Epileptiform Discharges in the Rat Limbic System In Vitro

Abstract: Application of 4-aminopyridine (4AP, 50 microM) to combined slices of adult rat hippocampus-entorhinal cortex-induced ictal and interictal epileptiform discharges, as well as slow field potentials that were abolished by the mu-opioid agonist [D-Ala2,N-Me-Phe4,Gly-ol5] enkephalin (DAGO, 10 microM) or the GABAA receptor antagonist bicuculline methiodide (BMI, 10 microM); hence, they represented synchronous GABA-mediated potentials. Ictal discharges originated in the entorhinal cortex and propagated to the hippocampus, whereas interictal activity of CA3 origin was usually recorded in the hippocampus. The GABA-mediated potentials had no fixed site of origin or modality of propagation; they closely preceded (0.2-5 sec) and thus appeared to initiate ictal discharges. Only ictal discharges were blocked by the antagonist of the NMDA receptor 3,3-(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP, 10 microM), whereas the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) abolished all epileptiform activities. The GABA-mediated potentials continued to occur synchronously in all regions even after concomitant application of CNQX and CPP. [K+]o elevations were recorded in the entorhinal cortex during the ictal discharge (peak values = 13.9 +/- 0.9 mM) and the synchronous GABA-mediated potentials (peak values = 4.2 +/- 0.1 mM); the latter increases were presumably attributable to postsynaptic GABAa-receptor activation because they were abolished by DAGO or BMI. Their role in initiating ictal activity was demonstrated by using DAGO, which abolished both GABA-mediated synchronous potentials and ictal discharges. These data indicate that NMDA-mediated ictal discharges induced by 4AP originate in the entorhinal cortex; such a conclusion is in line with clinical evidence obtained in temporal lobe epilepsy patients. 4AP also induces GABA-mediated potentials that spread within the limbic system when excitatory transmission is blocked and may play a role in initiating ictal discharge by increasing [K+]o.

An activating mutation of the follicle-stimulating hormone receptor autonomously sustains spermatogenesis in a hypophysectomized man.

Abstract: As both gonadotropins, LH and FSH, are required for normal spermatogenesis, patients with pituitary insufficiency need hCG plus human menopausal gonadotropin therapy to induce spermatogenesis and establish fertility. In a patient hypophysectomized because of a pituitary tumor, who, despite undetectable serum gonadotropin levels, had normal testis volume and semen parameters and fathered three children under testosterone substitution alone, we hypothesized an activating mutation of the FSH receptor. Exon 10 of the FSH receptor gene was amplified from genomic DNA by PCR, screened by single stranded conformation polymorphism gel electrophoresis, and sequenced. We identified a heterozygous A-->G base change at nucleotide position 1700, leading to an Asp-->Gly transition in codon 567 in the third intracytoplasmatic loop. COS-7 cells transiently transfected with the mutated receptor displayed a 1.5-fold increase in basal cAMP production compared to wild-type receptor, indicating that this mutation leads to liga...

Formation of intracytoplasmic lipid inclusions by Rhodococcus opacus strain PD630.

Abstract: An oleaginous hydrocarbon-degrading Rhodococcus opacus strain (PD630) was isolated from a soil sample. The cells were able to grow on a variety of substrates and to produce large amounts of three different types of intracellular inclusions during growth on alkanes, phenylalkanes, or non-hydrocarbon substrates. Electron microscopy revealed large numbers of electron-transparent inclusions with a sphere-like structure. In addition, electron-dense inclusions representing polyphosphate and electron-transparent inclusions with an elongated disc-shaped morphology occurred in small amounts. The electron-transparent inclusions of alkane- or gluconate-grown cells were composed of neutral lipids (98%, w/w), phospholipids (1.2%, w/w), and protein (0.8%, w/w). The major component of the cellular inclusions was triacylglycerols; minor amounts of diacylglycerols and probably also some free fatty acids were also present. Free fatty acids and/or fatty acids in acylglycerols in cells of R. opacus amounted up to 76 or 87% of the cellular dry weight in gluconate- or olive-oil-grown cells, respectively. The fatty acid composition of the inclusions depended on the substrate used for cultivation. In cells cultivated on n-alkanes, the composition of the fatty acids was related to the substrate, and intermediates of the β-oxidation pathway, such as hexadecanoic or pentadecanoic acid, were among the acylglycerols. Hexadecanoic acid was also the major fatty acid (up 36% of total fatty acids) occurring in the lipid inclusions of gluconate-grown cells. This indicated that strain PD630 utilized β-oxidation and de novo fatty acid biosynthesis for the synthesis of storage lipids. Inclusions isolated from phenyldecane-grown cells contained mainly the non-modified substrate and phenylalkanoic acids derived from the hydrocarbon oxidation, such as phenyldecanoic acid, phenyloctanoic acid, and phenylhexanoic acid, and approximately 5% (w/w) of diacylglycerols. The lipid inclusions seemed to have definite structures, probably with membranes at their surfaces, which allow them to maintain their shape, and with some associated proteins, probably involved in the inclusion formation.

Etiology of dental erosion – intrinsic factors

Abstract: Dental erosion due to intrinsic factors is caused by gastric acid reaching the oral cavity and the teeth as a result of vomiting or gastroesophageal reflux. Since clinical manifestation of dental erosion does not occur until gastric acid has acted on the dental hard tissues regularly over a period of several years, dental erosion caused by intrinsic factors has been observed only in those diseases which are associated with chronic vomiting or persistent gastroesophageal reflux over a long period. Examples of such conditions include disorders of the upper alimentary tract, specific metabolic and endocrine disorders, cases of medication side-effects and drug abuse, and certain psychosomatic disorders, e.g. stress-induced psychosomatic vomiting, anorexia and bulimia nervosa or rumination. Based on a review of the medical and dental literature, the main symptoms of all disorders which must be taken into account as possible intrinsic etiological factors of dental erosion are thoroughly discussed with respect to the clinical picture, prevalence and risk of erosion.

Cantilever dynamics in quasinoncontact force microscopy: Spectroscopic aspects

Abstract: The high-amplitude dynamic response of cantilever structures as used in scanning force microscopy was investigated as a function of the probe-sample distance. A computer simulation using the Muller-Yushchenko-Derjaguin/Burgess-Hughes-White (MYD/BHW) method applying realistic surface potentials including adhesion was done. The simulation providing dynamic force-distance curves allows us to attribute discontinuities observed in experimental amplitude-distance curves as the transition points from the purely attractive regime to the repulsive interaction near the lower inflection point of the vibrating probe. \textcopyright{} 1996 The American Physical Society.

Ultrasonic determination of gingival thickness. Subject variation and influence of tooth type and clinical features.

Abstract: The objectives of the present study were (I) to determine the validity and reliability of measuring gingival thickness (GTH) with a recently developed, commercially available ultrasonic device: (II) to measure GTH in relation to tooth type and age of proband;(III) to correlate GTH with varying forms of pre-molars, canines and incisors. Ultrasonic measurements were performed in 200 periodontally healthy, male probands representing 3 different age groups (20–25, 40–45, 55–60 years). In the maxilla, mean GTH varied between 0.9 mm (canines, 1st molars) and 1.3 mm (2nd molars). In the mandible respective mean values ranged between 0.8 mm (canines) and 1.5 mm (2nd molars). No differences in means and standard deviations (0.36–0.39 mm) were observed in different age groups. In order to correlate GTH with other clinical parameters and form of tooth, in 42 probands of the youngest age group, presenting with no attrition or abrasion, no artificial crown restorations and (following prophylaxis) no overt gingivitis and no periodontal probing depth in excess of 3 mm. detailed clinical measurements and stone model cast analyses were performed. By stepwise multiple linear regression analysis, 24% (p < 0.0001) of the variation of GTH was explained by probing depth, recession, width of gingiva and tooth type. The ratio of the width of the crown to its length was not included into the model. When performing analysis of covariance with the subject as factor, the model was improved, now explaining 41% of the variation of GTH. In this model, the influence of periodontal probing depth was decreased, and recession was not included. It was concluded that there are individual differences in GTH (i.e., different biotypes). However, thickness mainly depends on tooth type and is correlated with width of gingiva. There appears to be no association with shape and form of the tooth. Validity and reliability of measuring GTH with the ultrasonic device was found to be excellent.

Trans unsaturated fatty acids in bacteria

Abstract: The occurrence of trans unsaturated fatty acids as by-products of fatty acid transformations carried out by the obligate anaerobic ruminal microflora has been well known for a long time. In recent years, fatty acids with trans configurations also have been detected in the membrane lipids of various aerobic bacteria. Besides several psychrophilic organisms, bacteria-degrading pollutants, such as Pseudomonas putida, are able to synthesize these compounds de novo. In contrast to the trans fatty acids formed by rumen bacteria, the membrane constituents of aerobic bacteria are synthesized by a direct isomerization of the complementary cis configuration of the double bond without a shift of the position. This system of isomerization is located in the cytoplasmic membrane. The conversion of cis unsaturated fatty acids to trans changes the membrane fluidity in response to environmental stimuli, particularly where growth is inhibited due to the presence of high concentrations of toxic substances. Under these conditions, lipid synthesis also stops so that the cells are not able to modify their membrane fluidity by any other mechanism.

Self-interaction and relaxation-corrected pseudopotentials for II-VI semiconductors.

Abstract: We report the construction of pseudopotentials that incorporate self-interaction corrections and electronic relaxation in an approximate but very efficient, physically well-founded, and mathematically well-defined way. These potentials are particularly useful for II-VI compounds which are distinguished by their highly localized and strongly bound cationic semicore d electrons. Self-interaction corrections to the local-density approximation (LDA) of density-functional theory are accounted for in the solids to a significant degree by constructing appropriate self-interaction-corrected (SIC) pseudopotentials that take atomic SIC contributions into account. In this way translational symmetry of the Hamiltonian is preserved. Without increasing the complexity of the numerical calculations we approximately account, in addition, for electronic relaxation in the solids by incorporating into our pseudopotentials relevant relaxation in the involved atoms. By this construction we arrive at very useful self-interaction and relaxation-corrected pseudopotentials and effective one-particle Hamiltonians which constitute the basis for ab initio LDA calculations yielding significant improvements in electronic properties of II-VI compound semiconductors and their surfaces. The procedure is computationally not more involved than any standard LDA calculation and, nevertheless, overcomes to a large extent the well-known shortcomings of ``state of the art'' LDA calculations employing standard pseudopotentials. Our results for electronic and structural properties of II-VI compounds agree with a whole body of experimental data. \textcopyright{} 1996 The American Physical Society.

Translational Machinery in Dendrites of Hippocampal Neurons in Culture

Abstract: In neurons, several mRNAs are selectively delivered to dendritic domains where they are presumably translated by local protein synthetic machinery. Although electron microscopy has identified polyribosomes in dendrites, in particular in postsynaptic dendritic compartments, the functional composition of the local protein synthetic apparatus and the scope of its translational capacity have not been analyzed. To ascertain the translational competence of dendrites, we have probed hippocampal neurons in primary culture for various integral and associated factors of the translational apparatus. We report here that dendrites of such neurons are equipped with a spectrum of translational machinery components, including ribosomes, tRNAs, initiation and elongation factors, and elements of the cotranslational signal recognition mechanism. These components are differentially and nonuniformly distributed in dendritic arbors. Their dendritic location illustrates the soma-independent potential of dendrites to synthesize selected proteins in local domains.